title: Induction of toxins in Clostridium difficile is associated with dramatic changes of its metabolism.
abstract: Certain amino acids, and cysteine in particular, promptly blocked toxin expression in Clostridium difficile strain VPI 10463 when added to late-exponential-phase peptone-yeast cultures, i.e. prior to normal induction of toxins A and B. Glucose reduced toxin yields by 80-fold, but only when supplemented at inoculation. Forty upregulated C. difficile proteins were identified during maximum toxin expression, and most of these were enzymes involved in energy exchange, e.g. succinate, CO/folate and butyrate metabolism. Transcription of tcdA (toxin operon) and folD (CO/folate operon) was induced by 20- and 10-fold, respectively, and with strikingly similar kinetics between OD 0.8 and 1.2. The sigma factors tcdR and sigH were upregulated simultaneously with tcdA and folD (3.5-fold increase of mRNA level), whereas transcription of tcdC, codY, sigB and sigL showed little or no correlation with that of tcdA and folD. The results suggest a connection between toxin expression, alternative energy metabolism and initial sporulation events in C. difficile.
authors.affiliation: Karolinska Institute, Microbiology and Tumor Biology Center, S-171 77 Stockholm, Sweden.|Swedish Institute for Infectious Disease Control, Department of Bacteriology, S-171 82 Solna, Sweden.
authors.forename: Sture
authors.initials: S
authors.lastname: Karlsson
authors.affiliation: Swedish Institute for Infectious Disease Control, Department of Bacteriology, S-171 82 Solna, Sweden.
authors.forename: Lars G
authors.initials: LG
authors.lastname: Burman
authors.affiliation: Swedish Institute for Infectious Disease Control, Department of Bacteriology, S-171 82 Solna, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Åkerlund
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics*; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics*; D016360:Clostridioides difficile / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005947:Glucose / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005947:Glucose